Multi-Center in-Depth Screening of Neonatal Deafness Genes: Zhejiang, China.

Purpose: The conventional genetic screening for deafness involves 9-20 variants from four genes. This study expands screening to analyze the mutation types and frequency of hereditary deafness genes in Zhejiang, China, and explore the significance of in-depth deafness genetic screening in newborns.

Methods: This was a multi-centre study conducted in 5,120 newborns from 12 major hospitals in the East-West (including mountains and islands) of Zhejiang Province. Concurrent hearing and genetic screening was performed. For genetic testing, 159 variants of 22 genes were screened, including , , , , , , , , , , , , , , , , , , , , , and using next-generation sequencing. Newborns who failed to have genetic mutations or hearing screening were diagnosed audiologically at the age of 6 months.

Results: A total of 4,893 newborns (95.57%) have passed the initial hearing screening, and 7 (0.14%) have failed in repeated screening. Of these, 446 (8.71%) newborns carried at least one genetic deafness-associated variant. High-risk pathogenic variants were found in 11 newborns (0.21%) (nine homozygotes and two compound heterozygotes), and eight of these infants have passed the hearing screening. The frequency of mutations in , , , , and was 5.43%, 0.59%, 1.91%, 0.98%, and 0.02%, respectively. The positive rate of in-depth screening was significantly increased when compared with 20 variants in four genes of traditional testing, wherein was increased by 97.2%, by 21% and by 150%. The most common mutation variants were GJB2c.235delC and SLC26A4c.919-2A > G, followed by GJB2c.299_300delAT. Homoplasmic mutation in was the most common, including m.1555A > G, m.961T > C, m.1095T > C. All these infants have passed routine hearing screening. The positive rate of mutation was significantly higher in newborns with high-risk factors of maternal pregnancy.

Conclusion: The positive rate of deafness gene mutations in the Zhejiang region is higher than that of the database, mainly in GJB2c.235delC, SLC26A4 c.919-2A > G, and m.1555A > G variants. The expanded genetic screening in the detection rate of diseasecausing variants was significantly improved. It is helpful in identifying high-risk children for follow-up intervention.